The vast majority of analgesic research has focused on pharmacological agents, addressing particularly the peripheral and spinal cord mechanisms of opioid and anti-inflammatory therapy. It is now recognized, however, that a variety of modulatory mechanisms exists in the nervous system, and more importantly, that many of these endogenous pathways can be accessed through cognitive manipulations. The proposed research investigates a number of cognitive factors that modulate pain perception, examines their interrelationships, and explores possible cerebral mechanisms underlying their action. Study 1 will test the hypothesis that emotional context influences pain perception independent of attentional factors. Psychophysical studies in normal human subjects will employ cross-modality attention tasks, hedonically charged olfactory stimuli (to modify emotional context), and noxious heat as a painful stimulus. Functional magnetic resonance imaging (fMRl) will subsequently examine cerebral activation associated with these cognitively activated pain-modulatory systems. Study 2 will test the general hypothesis that cognitive modulation of pain perception is more pronounced for visceral than for cutaneous stimuli, as suggested by clinical evidence indicating a strong influence of emotional state on chronic visceral pain, such as the pain of irritable bowel syndrome or non-cardiac chest pain. This study will address the issue experimentally, using psychophysical and fMRl testing to compare directly the influence of emotional context and/or attentional state on sensory and affective aspects of visceral and cutaneous pain perception in normal human subjects. Finally, based on recent suggestions of gender dissimilarities in endogenous pain-modulatory systems, we will examine, in the above studies, sex-related differences in the modulatory influences of emotional context and attention on both the sensory and affective dimensions of pain perception. The influence of a patient's cognitive state on pain has been largely ignored in western medicine. Results of the proposed studies may help educate both physicians and patients about cognitive effects on pain and guide future development of cognitive strategies for pain control.